Anatomic Burden Predicts Outcome in Stable CAD

Action Points

Anatomic burden, but not ischemic burden, is a good predictor of outcomes in patients with stable coronary artery disease treated with optimal medical therapy with or without revascularization.

Point out that neither risk stratification measure, used alone or in combination, helped identify patients who would benefit from percutaneous coronary intervention (PCI) in addition to medical therapy.

Anatomic burden, but not ischemic burden, is a good predictor of outcomes in patients with stable coronary artery disease treated with optimal medical therapy with or without revascularization, findings from a substudy of the COURAGE trial revealed.

But neither risk stratification measure, used alone or in combination, helped identify patients who would benefit from percutaneous coronary intervention (PCI) in addition to medical therapy, according to the analysis, published online Wednesday in the journal JACC: Cardiovascular Interventions.

"In these patients who had the full-court press, with the full range of available medical treatments and angioplasty when symptoms warranted, baseline level of ischemia did not predict risk, whereas a low ejection fraction or the amount of coronary disease continued to do so throughout the trial," lead researcher G.B. John Mancini, MD, of the University of British Columbia in Vancouver, told MedPage Today.

COURAGE Questions PCI Benefit

The original COURAGE trial included 2,287 patients with stable myocardial ischemia and significant CAD randomized to optimal medical therapy (OMT) alone or OMT with PCI. The surprising finding was that adding PCI to medical management did not reduce the risk of death, myocardial infarction (MI) or other major cardiovascular events over 4 1/2 years of follow-up.

Almost from the moment of the study's publication in the spring of 2007, investigators have been trying, without success, to identify a subset of CAD patients who would clearly benefit from early elective angioplasty, Mancini said. "Ours is just one of a series of studies that once again shows that we have not found these patients."

The main objective of the substudy, however, was to determine the relative utility of anatomic burden and ischemic burden of CAD for predicting death and other major events.

The analysis included 313 patients from the original study treated with OMT plus PCI, and 308 patients treated with OMT alone. All patients underwent quantitative nuclear single-photon emission computed tomography (SPECT) to measure ischemic burden and angiography to measure left ventricular ejection fraction (LVEF) at baseline.

Multiple logistic survival analyses were performed to determine independent predictors of death, MI or non-ST-segment elevation acute coronary syndrome. LVEF was included in the analyses to account for the effects of irreversible ventricular damage and irreversible ischemia that would otherwise confound the interpretation of the nuclear and angiographic assessments, the researchers wrote.

LVEF, Anatomic Burden Predict Death

During a mean follow up of 4.69 years, 185 events occurred among the 621 patients included in the substudy (overall event rate of 30.3%).

In both non-adjusted and adjusted regression models, anatomic burden and LVEF were consistent predictors of death, MI and non-ST-segment elevation acute coronary syndromes, while ischemic burden and treatment assignment were not.

There was a marginal (P=0.03) effect of the interaction term of anatomic and ischemic burden for the prediction of clinical outcomes, but neither anatomy nor ischemia interacted with the therapeutic strategy to predict outcomes.

"I believe the findings here proved good news and bad news for the ISCHEMIA trial," King wrote.

He noted that patients in the ongoing trial will have a greater anatomic burden than most of the patients in the COURAGE trial due to the enrollment protocol, so they may have a better chance of benefiting from revascularization.

That's the good news.

"On the other hand, the bad news," he wrote. "Because there is no anatomic burden of disease used in the eligibility for the trial, some patients with the greatest predictive risk of events may be excluded. Others with extensive ischemia but less compelling anatomic burden may be included."

Outside the trial setting, the findings "raise important questions concerning algorithms for investigation of patients with stable ischemic heart disease," King wrote.

"Should angiograms be restricted to patients with higher risk scores from noninvasive evaluations of ischemia, or should some be considered for angiography? What will the future role of computed tomographic angiography be in these patients?," he asked, adding that the COURAGE substudy "raises the possibility that form (anatomic burden) may sometimes trump function (ischemic burden) in predicting cardiovascular events."

Funding was provided by the Cooperative Studies Program of the U.S. Department of Veterans Affairs Office of Research and Development, in collaboration with the Canadian Institutes of Health Research and by unrestricted research grants from Merck & Co., Pfizer, Bristol-Myers Squibb, Fujisawa, Kos Pharmaceuticals, Datascope, AstraZeneca, Key Pharmaceutical, Sanofi-Aventis, First Horizon, and GE Healthcare, including in-kind support with the U.S. FDA-approved drugs used by the study participants.

Dr. Mancini has received honoraria from Merck Canada and AstraZeneca and consulting fees from Sanofi-Aventis, GlaxoSmithKline, and Amgen. Dr. Berman has received grants from Lantheus Medical Imaging, Astellas Healthcare, GE Healthcare, Siemens, Cardium Therapeutics, Spectrum Dynamics, Applied Proteomics, and Bayer HealthCare and royalties from Cedars-Sinai (software) and has equity interest in Spectrum Dynamics. Dr. Chaitman has received consulting fees from Pfizer, Merck & Co., Roche, Sanofiaventis, Lilly, Gilead, and Forest and speaker fees from Gilead. Dr. Spertus has received grants from Lilly, Genentech, EvaHeart, and Gilead and consulting fees from Genentech, Amgen, Novartis, and Janssen and holds the copyright to the Seattle Angina Questionnaire

Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner

MedPageToday is a trusted and reliable source for clinical and policy coverage that directly affects the lives and practices of health care professionals.

Physicians and other healthcare professionals may also receive Continuing Medical Education (CME) and Continuing Education (CE) credits at no cost for participating in MedPage Today-hosted educational activities.